Idiopathic vaginitis accounts for up to 2 million visits to health care providers each year. This syndrome is characterized by vaginal itching, burning, discharge and discomfort not attributed to yeast, bacterial vaginosis or trichomoniasis. Our proposed research will focus on two potential mechanisms of disease: (1) novel vaginal microbes (bacterial or fungal) or (2) host mucosal immune activation. Although this is a well-described clinical phenotype that is frustrating for patients and clinicians alike, the underlying pathophysiology has not been evaluated. We will use deep sequencing to identify the bacterial and fungal communities present in the vagina of women with idiopathic vaginitis and will compare these with healthy women to determine whether there is a microbial signature associated with these symptoms. We will also evaluate the hypothesis that idiopathic vaginitis is an atypical immune response to otherwise normal vaginal microbiota, similar to atopic dermatitis or asthma. We will evaluate the mucosal immune activation profile in these women, specifically assessing whether inflammation is related to an atopic, Th2-type response to normal microbiota versus an innate immune activation due to bacterial antigens. Self-treatment of vaginitis symptoms is associated with over 500 million dollars in sales of over-the-counter medications. Women with idiopathic vaginitis experience significant psychologic distress, sexual dysfunction and depression. Identifying a target pathogen or immunologic pathway would make a significant contribution to the medical management of women with idiopathic vaginitis, with potential to relieve the significant distress associated with the lack of diagnostic or treatment options and to decrease the burden on the health care system related to multiple repeat visits for this condition.